Atherosclerosis is likely a chronic inflammatory disease associated with oxidation of lipoproteins. In order to investigate the effect of an estrogen with antioxidant potential on soluble markers of chronic vascular inflammation, we administered 17beta-estradiol to postmenopausal women, with measurement of cell adhesion molecules that tether and incorporate circulating inflammatory cells into the vessel wall. Twenty women were randomized to begin one-month treatment with either transdermal 17beta-estradiol 0.1 mg daily (9 women) or 17beta-estradiol 0.1 mg and medroxy-progesterone acetate 2.5 mg daily (11 women). We measured soluble E-selectin, intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) concentrations in serum, and the oxidizability of low density lipoprotein isolated from plasma (spectrophotometric diene formation assay) at baseline and following one month of treatment, with blinded performance of all assays. Hormone therapy significantly prolonged the time to onset of low density lipoprotein oxidation compared with pretreatment values (77+/-13 to 88+/-16 min, p=.003) and marginally reduced the maximum rate of oxidation (p=.077). Hormone therapy significantly lowered ICAM-1 levels by 8% (p=.009) and tended to lower E-selectin levels by 6% (p=.096) and VCAM-1 levels by 6% (p=.084). Co-administration of medroxyprogesterone acetate did not show any significant differences in the relative changes in E-selectin, ICAM-1 and VCAM-1 levels, compared to 17beta-estradiol alone (all p<.10). We conclude that hormone therapy has a favorable effect on markers of vascular inflammation, changes that may reduce the coronary artery disease risk of postmenopausal women.